System and method of adventitial tissue characterization

ABSTRACT

Disclosed herein is a system and method for characterizing adventitial tissue. In one aspect, a system and method are disclosed that characterizes tissue types within the adventitial tissue including nerve bundles and blood vessels. In a further aspect, the adventitia is imaged and characterized to provide guidance for crossing lesions within an occluded vessel.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a continuation U.S. patent application Ser.No. 16/285,869, filed Feb. 26, 2019, now U.S. Pat. No. 10,786,225, whichis a continuation of U.S. patent application Ser. No. 15/457,795, filedMar. 13, 2017, now U.S. Pat. No. 10,231,698, which is a continuation ofU.S. patent application Ser. No. 14/212,451, filed Mar. 14, 2014, nowU.S. Pat. No. 9,592,027, which claims priority to and the benefit ofU.S. Provisional Patent Application No. 61/784,570, filed Mar. 14, 2013,which are hereby incorporated by reference in their entireties.

FIELD OF THE INVENTION

The present disclosure relates generally to tissue characterization andmore particularly to procedures utilization tissue characterization ofthe adventitial tissues.

BACKGROUND

Intravascular tissue characterization is currently performed inconjunction with the evaluation of lesions within the lumens of vessels.Such characterization generally evaluates the properties of the lesionand provides a graphic display of the tissue types for the user. Exampleof such tissue characterization techniques are disclosed in U.S. Pat.Nos. 7,627,156 and 7,789,834, each of which is hereby incorporated byreference in its entirety. While these systems have been sufficient atproviding information concerning properties of the lesion, there remainsa need to determine additional information about the vessel andsurrounding supportive tissue to evaluate vessel health and determineappropriate therapies. Such additional features can also considerfurther aspects about prosthetic devices positioned in the vasculature.

In addition, intravascular imaging systems have been developed toidentify the border between different layers within a vessel. Forexample, U.S. Pat. Nos. 7,463,759 and 8,233,718, each of which isincorporated herein by reference in its entirety, disclose techniquesfor determining the borders been various regions within the vessel.Although such techniques provide valuable information in manysituations, when occlusions have disrupted vessel layer boundaries orthe imaging device is not directed perpendicular to the boundaries, suchboundaries may be difficult or impossible to image. Thus, there remainsa need for better imaging techniques to provide additional informationconcerning the vessel walls.

The devices, systems, and methods disclosed herein overcome one or moreof the deficiencies of the prior art.

SUMMARY

In one aspect, the present disclosure provides a system and method forperforming tissue characterization of adventitial tissue of a vessel.Among other features, the adventitial tissue characterizationinformation can assist the user in one or more of the following:evaluation of the location of nerve bundles, evaluation of tissue to beablated, the amount of energy to utilize, the extent of the area to beablated, damage to adjacent tissue, the direction of the tissue to beablated, the depth of ablation, amount and direction of vasa vasorum,myocardium encroachment or positioning adjacent the adventitial tissue,and guidance across through occlusions within a vessel.

In one embodiment, the present disclosure provides a method thatincludes imaging a vessel including surrounding adventitial tissue andperforming tissue characterization on the adventitial tissue. Theresults of the adventitial tissue characterization can then be displayedto a user. In one aspect, the display is a colorized display overlaid onan intravascular ultrasound image. In another aspect, the image is athree dimensional model highlighted with color to illustrate structuresidentified within the adventitial tissue. In one aspect, the tissuecharacterization includes identifying nerve bundles within theadventitial tissue. In another aspect, the imaging includes imaging theadventitia and the perivascular supportive tissue surrounding an arteryand the identifying includes identifying nerve bundles within theperivascular tissue. In a further aspect, the method includesidentifying myocardial muscular tissue surrounding the vessel anddisplaying the location to a user. In another aspect, the tissuecharacterization includes identifying and displaying vasa vasorum withinthe adventitial tissue. In another further aspect, the tissuecharacterization includes identifying the transition of the medial toadventitial tissue and the location of the adventitial tissue.

In another aspect of the present disclosure, a method is provided forperforming a first imaging of the vessel and first tissuecharacterization of the adventitial tissue of the vessel, conducting atherapy on the vessel, performing a second imaging of the vessel andsecond tissue characterization of the adventitial tissue of the vessel,comparing the first and second tissue characterizations and displayingthe differences to the user. In one aspect, additional therapy can bedelivered based on the differences displayed to the user. In oneembodiment, the therapy is includes an ablation therapy. In anotherform, the therapy includes stenting within the vessel. In still afurther aspect, the time between delivery of the therapy and the secondimaging is a period of at least several days, and the differencesdisplayed illustrate changes to tissue within or around the stent and/orchanges to the stent structure itself.

In still a further aspect, the present disclosure provides a system foradventitial tissue characterization. The system includes a data base ofknown adventitial tissue patterns, a sensor for collecting imaging datafrom a vessel, and a processor configured to compare the sensor imagingdata to the data base of known adventitial tissue patterns and determinetissue characterizations within the adventitial tissues.

In yet a further aspect, the present disclosure provides a method forutilizing tissue characterization in image guided therapy. In oneaspect, the method includes positioning an imaging device and a therapydevice within the lumen of a vessel and imaging the vessel including theadventitial tissue surrounding at least a portion of the lumen. Themethod continues with performing tissue characterization on theadventitial tissue and displaying adventitial tissue characteristics toa use. The position of the therapy device can then be changed inresponse to the displayed adventitial tissue characteristics. In oneaspect, the method includes defining a longitudinal direction of thetherapy device and alerting to the user to the presence of adventitialtissue in the longitudinal direction of the therapy device. In still afurther aspect, the therapy device is a chronic total occlusion crossingdevice and the changing includes changing the longitudinal direction ofthe device. In yet a further aspect, the therapy device is an ablationdevice and the changing includes changing the longitudinal or radialposition of the ablation device within the vessel in response to theadventitial tissue characteristics.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory innature and are intended to provide an understanding of the presentdisclosure without limiting the scope of the present disclosure. In thatregard, additional aspects, features, and advantages of the presentdisclosure will be apparent to one skilled in the art from the followingdetailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate embodiments of the devices andmethods disclosed herein and together with the description, serve toexplain the principles of the present disclosure. Throughout thisdescription, like elements, in whatever embodiment described, refer tocommon elements wherever referred to and referenced by the samereference number. The characteristics, attributes, functions,interrelations ascribed to a particular element in one location apply tothose elements when referred to by the same reference number in anotherlocation unless specifically stated otherwise.

The figures referenced below are drawn for ease of explanation of thebasic teachings of the present disclosure only; the extensions of thefigures with respect to number, position, relationship and dimensions ofthe parts to form the preferred embodiment will be explained or will bewithin the skill of the art after the following description has beenread and understood. Further, the exact dimensions and dimensionalproportions to conform to specific force, weight, strength and similarrequirements will likewise be within the skill of the art after thefollowing description has been read and understood.

The following is a brief description of each figure used to describe thepresent invention, and thus, is being presented for illustrativepurposes only and should not be limitative of the scope of the presentinvention.

FIG. 1 is a schematic illustration of an adventitial tissuecharacterization system in accordance with one embodiment of the presentdisclosure.

FIG. 2 illustrates an exemplary method of characterizing a specimen topopulate a pattern recognition training database in accordance with oneembodiment of the present disclosure.

FIG. 3 is a diagrammatic, cross-sectional illustration of anunobstructed artery, showing vascular wall layers and perivascularsupportive tissue.

FIG. 4A is a transverse sectional illustration of the artery shown inFIG. 3 along the lines 4-4, with FIG. 4B being a partial enlarged viewof FIG. 4A.

FIG. 5 is a diagrammatic, perspective illustration of a blood vesselshowing nerve bundles extending within the perivascular tissue.

FIGS. 6A and 6B are cross sectional images taken along line 6-6 of FIG.5, where 6A is an intravascular ultrasound image and 6B is thecorresponding histology processed image with a MOVAT Pentachrome stain.

FIG. 7 is a diagrammatic, cross-sectional illustration of a partiallyobstructed artery.

FIGS. 8A and 8B are angiographic images illustrating the effect ofmyocardial bridging on coronary arteries.

FIGS. 9A and 9B are diagrammatic, cross-sectional images of the coronaryartery of FIG. 8A.

FIG. 10 is a diagrammatic, cross-sectional view of a stent disposed in avessel.

FIGS. 11A-11C illustrate axial cross-sectional views taken through thestent of FIG. 10 showing initial implantation conditions on the left andnew conditions of the stent after a significant period of implantationon the right.

FIG. 12A illustrates an artery with a total occlusion and a catheter forimaging the occlusion, along with FIG. 12B showing the image of theocclusion generated by the catheter system.

FIG. 13A illustrates an artery with a total occlusion and a catheter forimaging the occlusion, along with FIG. 13B showing the image of theocclusion generated by the catheter system.

FIGS. 14A and 14B Illustrate a further forward looking imaging systemand the resultant display according to another aspect of the presentdisclosure.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of the disclosure is intended. Any alterations and furthermodifications to the described devices, instruments, methods, and anyfurther application of the principles of the present disclosure arefully contemplated as would normally occur to one skilled in the art towhich the disclosure relates. In particular, it is fully contemplatedthat the features, components, and/or steps described with respect toone embodiment may be combined with the features, components, and/orsteps described with respect to other embodiments of the presentdisclosure. For simplicity, in some instances the same reference numbersare used throughout the drawings to refer to the same or like parts.

The present disclosure relates generally to an apparatus, systems, andmethods for image-guided diagnostic procedures and monitoring of therapydelivery procedures through adventitial tissue characterization. Thepresent disclosure describes systems and methods for tissuecharacterization by analyzing images created by an energy emissiondevice, such as, by way of non-limiting example, an ultrasoundtransducer, deployable with an imaging system to facilitateinterpretation of images of vessel adventitial tissues, includingablated and neighboring tissue. The systems and methods described hereincorrelate image properties of the adventitial tissue with pre-determinedtissue properties to automatically and reproducibly characterize theadventitial tissues in real time (i.e., as the tissues are being imagedand/or ablated). By automatically and reproducibly characterizing theadventitial tissues in real time, the systems and methods describedherein minimize the known observer-variability associated with tissuecharacterization by observers. As used herein, unless expresslyindicated otherwise, the adventitial tissues being referred to andcharacterized are the tissue layers immediately outside the media alongwith the perivascular supportive tissues surrounding the adventitia thatinclude various intermingled tissue types generally within about 3-5 mmof the media that can include nerves, nerve bundles, blood vessels,muscle fibers (especially in the coronary arteries), connective tissue,fibroblasts and fat cells.

FIG. 1 illustrates an imaging system 100. The system 100 includes acatheter 110 comprising an elongate, flexible, tubular body 120 that isconfigured for intravascular placement and defines an internal lumen125. The body 120 extends from a handle 130 along a longitudinal axisCA, which is coupled to an interface 140 by an electrical connection145. The body 120 includes a proximal portion 150 and a distal portion160. In FIG. 1, the distal portion 160 includes an ablative element 170and an imaging apparatus 180 positioned proximal to a distal tip 190.The ablative element 170 and imaging apparatus 180 are positioned on aproximal segment of the distal tip 190. In the pictured embodiment, theablative element 170 is positioned proximal to the imaging apparatus180. In other embodiments, the ablative element 170 is positioned distalto the imaging apparatus 180. Generally, the catheter 110 may beconfigured to take on any desired profile, which may depend upon thetype of ablative element, the type of imaging apparatus (e.g.,ultrasound, OCT, multi-modality, etc.), the desired application, or theparticular tissue of interest. In some embodiments, aspects of thecatheter 110 may be substantially similar to aspects of a catheterdisclosed in U.S. Publication 2011/0251487, titled “Apparatus and Methods for Intravascular Ultrasound Imaging and for Crossing Severe VascularOcclusions,” and published Oct. 13, 2011, which is incorporated byreference herein in its entirety.

The interface 140 is configured to connect the catheter 110 to a patientinterface module or controller 210, which may include a graphic userinterface (GUI) 215, such as a display or a touch screen. Morespecifically, in some instances the interface 140 is configured tocommunicatively connect at least the imaging apparatus 180 and theablative element 170 of the catheter 110 to a controller 210 suitablefor carrying out ablation and intravascular imaging. The controller 210is in communication with and performs specific user-directed controlfunctions targeted to a specific device or component of the system 100,such as the ablation catheter 110, the imaging apparatus 180, and/or theablative element 170.

The interface 140 may also be configured to include a plurality ofelectrical connections, each electrically coupled to the ablativeelement 170 via a dedicated conductor and/or a cable (not shown),respectively, running through the lumen 125 of the body 120. Such aconfiguration allows for a specific group or subset of electrodes on theablative element 170 to be easily energized with either monopolar orbipolar energy, for example. Such a configuration may also allow theablative element 170 to transmit data from any of a variety of sensorson the ablative element via the controller 210 to data display modulessuch as a GUI 215 and/or a processor 220. The interface 140 is coupledto an ablation source 225 via the controller 210, with the controller210 allowing energy to be selectively directed to the portion of thetarget tissue that is engaged by the ablative element 170.

In the pictured embodiment, the imaging apparatus 180 comprises anultrasound imaging transducer. The imaging apparatus 180 can take theform of any one of a number of known ultrasound imaging transducers,such as, for example and without limitation, a phased array, aforward-looking array, a mechanically steered sector array, a rotationaltransducer, a vector array, a forward-looking oscillator transducer or alinear array. For example, in some embodiments involving cardiacablation applications, the imaging apparatus comprises intracardiacechocardiography (ICE) or forward-looking ICE. The imaging apparatus hasan imaging field of view 223 that may or may not overlap with theablating field 221. In the pictured embodiment, the imaging field ofview 223 is shown overlapping with the ablating field 221, therebyallowing the user to image the tissue being ablated within the ablatingfield 221 in real-time.

It should be appreciated that while the exemplary embodiments herein aredescribed in terms of an ultrasonic imaging apparatus, or moreparticularly the use of IVUS data (or a transformation thereof) torender images of an object, the present disclosure is not so limited.Thus, for example, an imaging apparatus using backscattered data (or atransformation thereof) based on electromagnetic radiation (e.g., lightwaves in non-visible ranges such as Optical Coherence Tomography, X-RayCT, infrared spectroscopy, etc.) to render images of any tissue type orcomposition (not limited to vasculature, but including other human aswell as non-human structures) is within the spirit and scope of thepresent disclosure. Any form of imaging, measuring, and/or evaluationdevice (and resultant data) is within the spirit and scope of thepresent disclosure. Still further, while the system and techniques aredescribed in the context of an invasive ultrasound system, it will beappreciated that the system and method of conducting tissuecharacterization may be accomplished throughout the body whether tissuesare accessed through natural openings or through openings formed throughthe skin.

The controller 210 is connected to the processor 220, which is typicallyan integrated circuit with power, input, and output pins capable ofperforming logic functions, an imaging energy generator 222, and theablation source 225. The processor 220 may include any one or more of amicroprocessor, a controller, a digital signal processor (DSP), anapplication specific integrated circuit (ASIC), a field-programmablegate array (FPGA), or equivalent discrete or integrated logic circuitry.In some examples, processor 220 may include multiple components, such asany combination of one or more microprocessors, one or more controllers,one or more DSPs, one or more ASICs, or one or more FPGAs, as well asother discrete or integrated logic circuitry. The functions attributedto processor 220 herein may be embodied as software, firmware, hardwareor any combination thereof.

The processor 220 may include one or more programmable processor unitsrunning programmable code instructions for implementing the ablativemethods described herein, among other functions. The processor 220 maybe integrated within a computer and/or other types of processor-baseddevices suitable for a variety of intravascular applications, including,by way of non-limiting example, ablation, intravascular imaging, andtissue characterization. The processor 220 can receive input data fromthe controller 210, a memory 245, a tissue pattern recognition database250 usable for tissue characterization, accessory devices 240, theimaging apparatus 180, and/or the ablative element 170 directly or viawireless mechanisms. The processor 220 can interpret and use such inputdata to generate control signals to control or direct the operation ofthe catheter 110. In some embodiments, the user can program or directthe operation of the catheter 110 and/or the accessory devices 240 fromthe controller 210 and/or the GUI 215. In some embodiments, theprocessor 220 is in wireless communication with the imaging apparatus180 and/or the ablative element 170, and can receive data from and sendcommands directly to the imaging apparatus 180 and/or the ablativeelement 170.

In various embodiments, the processor 220 is a targeted devicecontroller that may be connected to a power source 230, accessorydevices 240, the memory 245, and/or the ablation source 225. In such acase, the processor 220 is in communication with and performs specificcontrol functions targeted to a specific device or component of thesystem 100, such as the imaging apparatus 180 and/or the ablativeelement 170, without utilizing user input from the controller 210. Forexample, the processor 220 may direct or program the imaging apparatus180 and/or the ablative element 170 to function for a period of timewithout specific user input to the controller 210. In some embodiments,the processor 220 is programmable so that it can function tosimultaneously control and communicate with more than one component ofthe system 100, including the accessory devices 240, the power source230, and/or the ablation source 225. In other embodiments, the systemincludes more than one processor and each processor is a special purposecontroller configured to control individual components of the system.

In the pictured embodiment, the controller 210 is configured to couplethe imaging apparatus 180 to the imaging energy generator 222. Inembodiments where the imaging apparatus 180 is an intravascularultrasound (IVUS) transducer(s), the imaging energy generator comprisesan ultrasound energy generator. Under the user-directed operation of thecontroller 210, the imaging energy generator 222 may generate a selectedform and magnitude of energy (e.g., a particular energy frequency) bestsuited to a particular application. At least one supply wire (not shown)passing through the body 120 and the interface 140 connects the imagingapparatus 180 to the imaging energy generator 222. The user may use thecontroller 130 to initiate, terminate, and adjust various operationalcharacteristics of the imaging energy generator 222.

The power source 230 may be a rechargeable battery, such as a lithiumion or lithium polymer battery, although other types of batteries may beemployed. In other embodiments, any other type of power cell isappropriate for power source 230. The power source 230 provides power tothe system 100, and more particularly to the processor 220. The powersource 230 may be an external supply of energy received through anelectrical outlet. In some examples, sufficient power is providedthrough on-board batteries and/or wireless powering.

The various peripheral devices 240 may enable or improve input/outputfunctionality of the processor 220. Such peripheral devices 240 include,but are not necessarily limited to, standard input devices (such as amouse, joystick, keyboard, etc.), standard output devices (such as aprinter, speakers, a projector, graphical display screens, etc.), aCD-ROM drive, a flash drive, a network connection, and electricalconnections between the processor 220 and other components of the system100. By way of non-limiting example, a processor may manipulate signalsfrom the imaging apparatus 180 to generate an image on a display device,may coordinate aspiration, irrigation, and/or thermal neuromodulation,and may register the treatment with the image. Such peripheral devices240 may also be used for downloading software containing processorinstructions to enable general operation of the catheter 110, and fordownloading software implemented programs to perform operations tocontrol, for example, the operation of any auxiliary devices attached tothe catheter 110. In some embodiments, the processor may include aplurality of processing units employed in a wide range of centralized orremotely distributed data processing schemes.

The memory or database 245 is typically a semiconductor memory such as,for example, read-only memory, a random-access memory, a FRAM, or a NANDflash memory. The memory 245 interfaces with processor 220 such that theprocessor 220 can write to and read from the memory 345. For example,the processor 220 can be configured to read data from the imagingapparatus 180 and write that data to the memory 345. In this manner, aseries of data readings can be stored in the memory 245. The processor220 is also capable of performing other basic memory functions, such aserasing or overwriting the memory 245, detecting when the memory 345 isfull, and other common functions associated with managing semiconductormemory. In the pictured embodiment, the memory 245 comprises a databaseof characterization data.

The tissue pattern recognition or characterization application 250 isadapted to receive data (e.g., imaging data) from the processor 220and/or the controller 210. The characterization application may exist asa single application or as multiple applications and be locally orremotely stored. In an exemplary embodiment, the characterizationapplication 250 is adapted to receive and store characterization data(e.g., tissue type, adventitial characteristics, ablationcharacteristics, stent characteristics, myocardium characteristics, andsecondary parameters or patterns). In particular, to create a databaseof characterization data, after a tissue specimen has been imaged andIVUS data has been collected, a histology correlation is prepared bycollecting, dissecting, and preparing the tissue specimen for slidereview (e.g., fixing and staining the tissue specimen with a processthat is well known in the art). Slide review allows a clinician toidentify and characterize the tissue type(s) and/or histologicalchemicals/markers (i.e., chemicals and/or markers associated withparticular tissue types) found within the specimen. It should be notedthat the particular method used to characterize the tissue specimen isnot a limitation of the present disclosure, and all tissue specimencharacterization methods generally known to those skilled in the art arewithin the scope of the present disclosure.

In one embodiment, the tissue specimen comprises a region of ablatedtissue. The tissue may be any of a variety of tissue types, including,by way of non-limiting example, muscle tissue, fatty tissue, fibroustissue, fibrolipidic tissue, vessel tissue (e.g., by way of non-limitingexample, compositional tissues such as vessel wall, luminal wall,medial-adventitial boundary, adventitial tissue, myocardium), neuraltissue, calcific tissue, necrotic tissue, calcified-necrotic tissue,collagen compositions, cholesterol deposits, and/or adventitial tissue.In addition, the tissue specimen can comprise ablated tissue in any of avariety of stages of ablation, including, by way of non-limitingexample, minimally ablated tissue, moderately ablated tissue, majorlyablated tissue, and/or completely ablated tissue. The characterizationdata gathered from the tissue specimens can include all otheridentifiable characteristics generally known to those of skill in theart. In some embodiments, tissue specimens having a full range ofvarying degrees of ablation per tissue type are interrogated (imaged andhistologically sectioned) for inclusion in the characterizationapplication 250.

The identified tissue type(s) and/or characterization conclusions areprovided to the characterization application 250 as characterizationdata. In some embodiments, the characterization data is provided via theGUI 215 or another input device that is electrically coupled to thecontroller 210 and/or the processor 220. The characterization data isthen stored in the memory or database 245.

In one embodiment, the characterization application 250 is adapted tocreate a histology image of the tissue specimen and to identify the atleast one corresponding region on an image (e.g., an IVUS image) of thetissue specimen. A region of interest (ROI) on the histology image(which may be provided to the characterization application 250 via theGUI 215 or another input device in the form of digitized data that isused to create the histology image) can then be identified by the user.The ROI may be characterized by the characterization data, and cancomprise the whole tissue specimen or only a portion thereof. Thecharacterization application is adapted to identify a correspondingregion on the scanned image (e.g., IVUS image).

In some instances, the histology image may need to be morphed or warpedto accurately match and substantially fit the contour of the IVUS image(thereby removing histological preparation artifacts). In someembodiments, therefore, the characterization application 250 is adaptedto morph or warp the histology image to accurately match the IVUS image.Specifically, the characterization application 250 is configured toidentify at least one landmark common to both the histology image andthe IVUS image and is adapted to use various algorithms to substantiallyalign the two images. The landmark may comprise an anatomic landmark(such as, by way of non-limiting example, side-branch vessels, a vesselwall, and a tumor border) or a marker (such as, by way of non-limitingexample, a suture tie or an inked mark). In one embodiment, thecharacterization application is adapted to use a first algorithm (e.g.,a morphometric algorithm) to substantially align the correspondinglandmarks and a second algorithm (e.g., a thin plate spline (TPS)deformation technique) to substantially align the non-landmark portionsof the object.

In one embodiment, the characterization application 250 is furtheradapted to determine and store at least one parameter associated withthe ROI portion of the IVUS image. In particular, the characterizationapplication 250 is adapted to identify the IVUS data (i.e., the rawbackscatter data) that corresponds to the ROI identified on the IVUSimage (i.e., the IVUS data that was originally used to create the ROI onthe IVUS image). Different types and densities of tissue absorb andreflect emitted energy differently. Each reflected signal ischaracteristic of the type of tissue and the condition of the tissuethat reflected it. Differences in the reflected signal along each pathcan be determined by performing analysis on the signals. As a result,identifying different signal characteristics along each reflected pathallows for a correlation to the type of tissue and the condition of thetissue associated with those particular signal characteristics. As willbe described below, the signal characteristics of each reflected signalcan serve as a signature for different types of components within thescanned tissue, including, for example and without limitation, necroticplaque components within an artery, adventitia, neural tissue, minimallyablated muscle tissue, or completely ablated neural tissue.

The at least one parameter is then stored in the memory 245, where it islinked to the characterization data associated with the ROI. Eachparameter may be associated with more than one tissue type or degree ofablation. For example, a first parameter may be common to multipletissue types and multiple degrees of ablation. In some embodiments,signal analysis (i.e., frequency analysis, etc.) is performed on theidentified IVUS data before the parameters are identified because thefrequency information can serve as a “signature” for a particular tissuetype or characteristic. The IVUS data may be converted or transformedinto the frequency domain to identify the specific frequency spectrum ofthe ROI. The characterization application 250 and this transformationprocess are described in further detail below with reference to FIG. 3.

It should be appreciated that the number and location of the componentsdepicted in FIG. 1 are not intended to limit the present invention, andare merely provided to illustrate an exemplary environment in which thecatheters, systems, and methods described herein may operate. Thus, forexample, a system having a plurality of databases and/or a remotelylocated characterization application is within the spirit and scope ofthis disclosure.

An exemplary method of populating the training database or memory 245 isillustrated in FIG. 2. Specifically, at step 300, IVUS data (i.e., RFbackscatter data) is collected from a portion of the specimen. This datais used to create an IVUS image, which may be a two-dimensional image ora three-dimensional image, at step 305. At step 310, the scanned portionof the specimen is dissected and/or cross-sectioned and a tissue type(and/or characterizations thereof) is identified. At step 315, thischaracterization data is transmitted to the tissue characterizationsystem 100. In particular, the characterization data may be transmittedto the memory 245 and/or the characterization application 250. Thecharacterization data may include a variety of identifying and/orcharacterization information, such as, for example and withoutlimitation, information about the type of tissue, the different cellcomponents within the tissue, particularly within the adventitialtissue, and the degree of ablation (e.g., varying cellular changes dueto ablation). As a further feature, IVUS data may be collected for anunablated ROI and compared to an existing database to obtain an initialcharacterization. Ablation energy can then be applied to the ROI tochange the nature of the tissue in the ROI. Then, the ROI tissue may bedissected and/or cross-sectioned. At step 320, an image of thecross-sectioned object is created and an ROI is identified (e.g., by auser and/or the processor 220). The image may be two-dimensional orthree dimensional. At step 325, this image may be morphed, if needed, tosubstantially match the cross-section image to the IVUS image formed atstep 305. This may include identifying and matching up at least onecommon landmark on the two images using an algorithm, as describedabove. At step 330, the ROI is mapped to the IVUS image and associatedIVUS data is identified. Image analysis (including, for example andwithout limitation, spectral analysis and frequency analysis) is thenperformed on the associated IVUS data at step 335, and at least oneparameter or pattern is identified at step 340. At step 345, the atleast one parameter and the characterization data is stored in thememory 245 and/or the characterization application 250. In someembodiments, the at least one parameter or pattern is stored such thatit is linked to the characterization data.

The process depicted in FIG. 2 is repeated for each tissue component orsection desired to be identified and/or characterized, and may berepeated for each component as many times as desired in order to obtainan accurate range of signal properties. Still further, in one aspect,tissue characterization is performed with a stent in place such that thecharacteristics of the stent can be accounted for in the images.

FIGS. 3, 4A, and 4B illustrate the layers of a normal artery 420. Theinnermost layer that defines the lumen 425 of the artery 420 comprisesthe intima 430. In a healthy artery, the intima is relatively thin. Asplaque develops and infiltrates the intima, it increases in thickness.Medial layers 435 surround the intima 430. The medial layers 435 includesmooth muscle tissue and provide structural integrity for the artery420. The medial layers are made up of three layers that include twoelastic layers, an inner elastic lamina 436 and an outer elasticmembrane 437, along with a thicker muscular media comprised of smoothmuscle cells 435. The outermost layer is the adventitia 440, whichtypically comprises fibrous tissue such as collagen, and has a poorlydefined outer boundary transitions to perivascular supportive tissue448. As shown in more detail in the enlarged partial vessel view shownin FIG. 4B, the adventitia includes a collagen material 441 interruptedby small blood vessels or arterioles 442, such as vasa vasorum or neovasa vasorum, that supply oxygen to the main artery wall and typicallyextend the inside the media or at the edge of the medial-adventitialborder. In higher numbers or size than normal, they are considered to beindicative of disease progression and vulnerability. In addition, nervebundles 443 and fibroblasts 444 also exist within the collagen material441. The perivascular tissue 448 surrounds at least a portion of theadventitia and can include various intermingled tissue types generallywithin about 3-5 mm of the media that can include nerves, nerve bundles443, blood vessels, muscle fibers 447 (especially in the coronaryarteries), connective tissue, fibroblasts and fat cells. As shown inFIG. 4b , some structures such as nerve bundle 443 can extend withinboth adventitia 440 and within perivascular tissue 448.

Referring more specifically to FIG. 4A, an imaging device 110 is shownpositioned within the vessel lumen 425. In traditional arterial tissuecharacterizations, the imaging device supplies return data concerningthe intima 430 (along with any plaques) and the media 438. However,approximately 45% of the nerves associated with a blood vessel can belocated by extending the tissue characterization outwardly to an initialarea designated as Zone 1. This includes the adventitia along with asmall portion of perivascular tissue. For example, in a large arteryhaving an internal diameter of 5 mm, such as a renal artery, Zone 1 mayextend to a radius A of approximately 3.5 mm or a 7.0 mm diameter. In afurther aspect, by expanding the tissue characterization area to includethe perivascular tissue of Zone 2, approximately 95% of the nerves andnerve bundles can be image and characterized. In the large artery havingan internal diameter of 5 mm, the Zone 2 diameter would extend toapproximately 11.0 mm with a radius B of approximately 5.5 mm. Asexplained more fully below, characterization of the tissue beyond theexternal elastic lamina or outer elastic membrane 437 providesadditional information that may assist in diagnosing and treating anynumber of vascular or neurologic diseases or conditions. As used herein,unless expressly indicated otherwise, the adventitial tissues beingreferred to and characterized are the tissue layers immediately outsidethe outer elastic membrane 437 along with the perivascular tissuessurrounding the adventitia that include various intermingled tissuetypes generally within about 3-5 mm of the outer elastic membrane thatcan include nerves, nerve bundles, blood vessels, muscles (especially inthe coronary arteries), connective tissue, fibroblasts and fat cells.

With reference back to FIG. 1, the data collected by the imagingapparatus 180 of the catheter 110 is initially in the form of raw dataof the reflected signals along each scan line. The data is then refinedor transformed into a format that can be analyzed by thecharacterization application 250 to determine various signalcharacteristics that may identify associated tissue types within andadjacent the scanned object 405. In the pictured embodiment, thecharacterization application 250 includes several component parts,including the memory or database 245, a signal analyzer logic, and acorrelation logic. The signal analyzer logic is configured to processand analyze the data to identify, in real-time, the various componentsof the scanned object 405. The signal analyzer logic is configured toidentify various types of tissue and/or tissue components and to providean assessment as to the content and health of the adventitia based onthe type of tissues and/or tissue components identified. In addition,adventitial tissue characterization can be performed before delivery ofa therapy, such as ablation, and after delivery of a therapy to providethe user with feedback on the impact of the therapy on the structures ofthe adventitia. Additional details concerning systems that provide bothimaging and therapy delivery can be found in U.S. ProvisionalApplication No. 61/745,476, filed Dec. 21, 2012, entitled: Device,System, and Method for Imaging and Tissue Characterization of AblatedTissue and U.S. Provisional Patent Application No. 61/733,738, filedDec. 5, 2012, entitled: System and Method for Non-Invasive TissueCharacterization, each of which is hereby incorporated by reference intheir entirety.

Referring now to the example shown in FIG. 5, the imaging apparatus 110is positioned within the lumen 425 of the vessel 450. The lumen 425 hasan internal diameter D1 and a vessel wall thickness extending between D1and the outer diameter D2. As explained above, the internal diameter D1can be approximately 5 mm and external diameter D2 can be approximately11 mm, making the wall thickness approximately 3 mm. In the illustratedexample, the vessel 450 is a renal artery with perivascular tissueincluding sympathetic renal nerves 443 extending along the vessel. Inaddition, smooth muscle cells 447 may also extend within theperivascular tissue. In embodiments using ultrasound imaging, thetransducers of the imaging apparatus 110 would be pulsed along scanlines and then acquire echoes of backscatter signals reflected from thetissue along each scan line. The backscatter signal is characteristic ofthe type of tissue (including the tissue composition and level ofablation if utilized) that reflected it. Differences in the backscattersignal along each scan line can be determined by performing a frequencyanalysis, using spectral analysis and autoregressive coefficients, awavelet decomposition, and/or a curvelet decomposition on the signals.As a result, identifying different signal characteristics along eachscan line allows for a correlation to the type of tissue and, in thepresence of ablation, a certain level of ablation associated with thoseparticular signal characteristics. As further described herein, signalcharacteristics of the backscattered signal can serve as a signature fordifferent types of components of the adventitial tissues of the vessel,including, for example, nerve bundles, blood vessels, myocardium orother muscle, and fibroblasts.

The signal properties of the transmit and receive signals are processedby the characterization application 250, which is configured tocorrelate the signal properties of the scan line segment with the typeof tissue component having those or similar signal properties. In thatregard, the characterization application 250 is configured to compareand match the signal properties to pre-determined or pre-generatedadventitial tissue signal properties contained within the memory ordatabase 245. Various parameters may comprise the database ofpre-determined tissue signal properties. The parameters comprising thedatabase 245 would be pertinent to both the desired application ortissue-of-interest and the imaging modality of the imaging probe (i.e.,ultrasound, OCT, spectroscopy, etc.). The characterization application250 is configured to recognize the type of imaging modality employed bythe imaging probe 110 and to use the appropriate pre-determined tissuesignal properties associated with that particular imaging modality. Forexample, if the imaging modality being used were ultrasound, thepre-determined signal properties may include various parameters in thespectral domain directly associated with scatter size, density,viscosity, and their acoustic properties such as impedance andattenuation coefficient. The pattern recognition training database alsocontains macro-data about overall characteristics, such as size, nervecell directionality, vasa vasorum directionality, morphology, as well aspatient demographic information such as age, gender, race and relevantmedical history, such as known diabetic, cardiovascular disease,hypertension information and others.

In some embodiments, the imaging system 100 may employ a multitude ofdifferent imaging modalities to image the same object such as bloodvessel 450. In some embodiments, these imaging modalities are usedsequentially, whereas in other embodiments, the different imagingmodalities are used simultaneously (e.g., using a multi-modality imagingapparatus). In one example, the imaging probe is first energized toimage the adjacent tissue of the vessel with a 40 MHz ultrasonic pulse.Following the first imaging pass of the probe, the imaging probe isenergized to image the adjacent tissue with a 20 MHz ultrasonic pulse.In such a system, the image data from both passes may be compared tocorresponding data in by the characterization application 250. In stilla further aspect, the imaging probe may be constructed to provide anddetect harmonic variations of the center frequency such that differentfrequencies can be detected within a single pulse. In still a furtherembodiment, the imaging probe 110 may be configured to image the objectusing a multitude of different imaging modalities (e.g., OCT andultrasound). In some embodiments, the characterization application 250is configured to combine or analyze the pre-determined signal propertiesand patterns associated with each imaging modality used to performadventitial tissue characterization.

Secondary parameters may be included within the data structure toreflect the type of tissue and/or the particular pre-existing conditionsor differential diagnoses of the patient. The secondary parameters maybe utilized by the correlation logic to more accurately compare andmatch the signal properties to the pre-determined signal properties 480.One secondary parameter may comprise the type of vessel being observed.For example, in larger vessels the vessel walls may be much thicker andthe overall diameter of the vessel may be much larger. Thus, it isanticipated that the imaging device may need to be positioned closer toone wall within a large vessel to perform adventitial tissuecharacterization on only a portion while in a smaller vessel, such as acoronary artery, it may be possible to perform adventitial tissuecharacterization on the full circumference of the adventitial tissue. Insome embodiments, the imaging system 100 can determine the type oftissue or anatomic region observed with the vessel and use this as asecondary parameter before automatically selecting the appropriatepre-determined signal properties associated with the type of tissue oranatomic region or appropriately adjusting the pre-determined signalproperties to reflect the type of tissue or anatomic region. In otherembodiments, the user may enter the type of tissue or anatomic regionmanually (e.g., via the GUI 215), and either the user or the imagingsystem 100 may select the appropriate pre-determined signal propertiesassociated with that type of tissue/region or appropriately adjust thepre-determined signal properties to reflect this type of tissue/region.For example, if the tissue being scanned includes a calcified vascularplaque, either the user or the imaging system 100 may select theappropriate pre-determined signal properties associated with calcifiedplaque tissue or appropriately adjust the pre-determined signalproperties to reflect changes observed for calcified plaque tissue. Insome embodiments, a three-dimensional data set can be constructed withthe imaging apparatus 110 to provide further parameters related totissue type and matched back to the secondary parameters in the database245 that contains these pre-determined ablation values for varioustissue types.

Another secondary parameter associated with the imaging may comprise theparticular frequency or harmonics employed by the imaging apparatus 110.For example, the database 245 may contain particular sets ofpre-determined signal properties associated with particulars frequenciesor harmonic patterns.

With reference again to FIG. 2, the data collected by the imagingapparatus 180 is initially in the form of raw ultrasound data of thebackscattered signals along each scan line. The ultrasound data is thenanalyzed to determine various signal characteristics that may identifyassociated tissue types. The signal analyzer logic is configured toprocess and analyze the data to identify, in real-time, the presence andcomponents of the adventitial tissue. Because different types anddensities of tissue absorb and reflect the ultrasound pulsesdifferently, the signal analyzer logic utilizes the reflectedbackscatter data to assemble a two-dimensional or three-dimensionalultrasound characterization of the adventitia from hundreds ofpulse/acquisition cycles. In this embodiment, the logic is configured toidentify various types of adventitial tissue, including vasa vasorum,nerve bundles, collagen matrix and strands of muscle cells (particularlyin the case of coronary arteries) within the adventitial tissue.

In one embodiment, the signal analyzer logic includes logic to transformthe data to the frequency domain and analyze frequency information ofthe signals to determine one or more signal properties. It will beappreciated that the signal analyzer logic may be embodied as part of anultrasound imaging console, an ablation system console, or as part of aseparate system that receives raw radio frequency data from anultrasound apparatus. If the radio frequency data is in analog form, adigitizer may be provided to digitize the data. A signal processinglogic is configured to process each scan line of the ultrasound data andtransform it to a format that can be analyzed. To reduce processingtime, a border detection or segmentation logic may be used to determinethe location of the borders of the object being scanned, particularlythe border between the media and the adventitia such that thecharacterization application 250 can focus on analyzing the echo returnsfrom adventitial tissue extending beyond the media including theperivascular tissues. Because the analysis is most interested in thecomponents of the adventitial tissue, scan line data outside of theadventitial tissue can be filtered and removed. One example of a borderdetection system is described in U.S. Pat. No. 6,381,350, entitled“Intravascular Ultrasonic Analysis Using Active Contour Method andSystem,” which is incorporated herein by reference for all purposes.

After border detection, the scan line data is transformed. Of course,border detection can be performed after transformation. Transformationlogic is configured to transform the remaining scan line data into aformat suitable for analysis. In general, the transformed format shouldmatch the same format used to build the pre-determined signal propertiesof the object component. In one embodiment, the transformation logictransforms the data to a power spectrum plot of frequency versus poweroutput. Various transformation algorithms include a Fouriertransformation, Welch periodograms, and auto-regressive modeling. Othertypes of transformations can include transforming the data to waveletsthat provide an image with frequency and time information. For example,other signal processing techniques may include wavelet decomposition orcurvelet decomposition to deliver parameters that are relevant fordiscrimination between tissue types while not being influenced by thesystem transfer function of the imaging system and probe. Anothertransformation includes using impedance, rather than frequency, whichgives an image of acoustic impedance. In this format, different tissuecomponents have different impedance properties that provide differentsignal reflections.

Referring to FIG. 2, a spectral analysis logic analyzes the powerspectrum of the scan line data to determine its spectral properties instep 335. As mentioned previously, spectral properties or parameters mayinclude maximum power, frequency at the maximum power, minimum power,the frequency at the minimum power, the slope, y-intercept, mid-bandfit, and integrated backscatter. The spectral parameters are identifiedin step 340 and are then inputted to a classification application 250that attempts to classify the spectral parameters associated to aparticular scan line segment with previously measured spectralparameters from a known tissue component. As mentioned above, the signalanalyzing techniques need not be limited to spectral analysis andautoregressive coefficients, but could entail use of waveletdecomposition or curvelet decomposition to deliver parameters that maybe used by the classification logic to discriminate between tissuetypes.

A variety of pattern recognition approaches may be used by theclassification logic and/or correlation logic. For example, the database245 of relevant secondary parameters and pre-determined tissue signalproperties could be the starting point of various pattern recognitionapproaches, covering, but not limited to, classification trees, randomforests, neural networks, regression trees, principal components, and/ora combination of these to arrive at an accurate tissue characterization.For example, in one embodiment, the pre-determined tissue signalproperties and/or the secondary parameters may be stored in the database245 as a classification tree or a regression tree having branch nodeconditions based on the pre-determined tissue signal properties and oneor more leaf nodes that identify a tissue component of adventitialtissue. In another embodiment, the pre-determined tissue signalproperties may be embodied in the database as an artificial neuralnetwork having one or more nodes that identify a tissue component ofadventitial tissue. In some embodiments, the classification logic and/orthe correlation logic may utilize a random forest classifier to analyzea number of classification trees (e.g., different classification treesbased on different pre-determined signal properties or based on amultitude of different imaging modalities) to arrive at a tissuecharacterization.

The characterization application 250 may be configured to reconstructthe received data into displayed 2D or 3D images, and the identifiedadventitia components may be visually distinguished on a displayassociated with the GUI 215. In some embodiments, a display may beincluded as a component of an imaging system console (not shown). Inother embodiments, the display may be an independently located devicethat communicates either wirelessly or through a wired connection withthe characterization system 100. In some embodiments, the display may beremotely located.

Referring now to FIGS. 6A and 6B, there are shown cross-sectional imagesof the vessel of FIG. 5 taken along line 6-6. FIG. 6A illustrates anexemplary IVUS image showing the inner lumen 445, nerve bundles 443 andmuscle fibers 447 disposed in the adventitial tissue. A pair of lineshas been inserted into the image to designate the boundary between themedia, adventitia 440 and perivascular tissues 447. In this depiction,the nerve bundles appear as hypoechoic regions within the adventitialtissues. It will be appreciated that prior to tissue characterization,many of the structures are difficult for a user to distinguish orinterpret. In one aspect, the appearance of some tissues depends on theangle of incidence of the ultrasound, such as nerve bundles and musclefibers, such that a plurality of images may need to be analyzed to morefully characterize the tissues. FIG. 6B illustrates a Movat'spentachrome stained histology section highlighting nerve bundles 443,and muscle fibers 447 in the adventitial perivascular tissue. Asexplained more fully above with respect to FIGS. 4A and 4B, most of thenerve bundles are located in the perivascular tissues that form theadventitial tissues being characterized. It will be appreciated thatafter tissue characterization, the tissue structures of the IVUS imagesmay be colorized on a display to better highlight these features for auser. The display may take the form of a colorized version of FIG. 6A.In an alternative form, the display may be a longitudinal cross sectionof the vessel, showing the adventitial tissues on either side of thevessel with color coding used to distinguish the various tissue types.In still a further form, a 3 or multi-dimensional model may beconstructed utilizing the tissue characterization data to display a 3 ormulti-dimensional model of the nerve bundle and or muscle fiberssurrounding the vessel. It will be appreciated that in one display mode,only the nerve tissue can be displayed in a 3 or multi-dimensionalmodel. This type of display can be particularly beneficial when combinedwith an ablation characterization system such that nerve ablation can bevisualized in a 3-dimensional model in real-time.

The imaging apparatus 100 in the pictured embodiment is an intravascularultrasound (IVUS) apparatus. The entire IVUS apparatus may extendthrough the body and include all the components associated with an IVUSmodule, such as a transducer(s), multiplexer(s), electricalconnection(s), etc., for performing IVUS imaging. The imaging apparatus100 of the pictured embodiment may utilize any IVUS configuration thatallows at least a portion of the body to be introduced over a guidewire.For example, in some instances, the imaging apparatus utilizes an arrayof transducers (e.g., 32, 64, 128, or other number transducers) disposedcircumferentially about the central lumen 925 of the body 920 in a fixedorientation. In other embodiments, the IVUS portion is a rotational IVUSsystem. In some instances, the imaging apparatus includes componentssimilar or identical to those found in IVUS products from VolcanoCorporation, such as the Eagle Eye® Gold Catheter, the Visions® PV8.2FCatheter, the Visions® PV 0.018 Catheter, the Visions® PV 0.035 Catheterand/or the Revolution® 45 MHz Catheter, and/or IVUS products availablefrom other manufacturers. Further, in some instances the catheter 850includes components or features similar or identical to those disclosedin U.S. Pat. Nos. 4,917,097, 5,368,037, 5,453,575, 5,603,327, 5,779,644,5,857,974, 5,876,344, 5,921,931, 5,938,615, 6,049,958, 6,080,109,6,123,673, 6,165,128, 6,283,920, 6,309,339; 6,033,357, 6,457,365,6,712,767, 6,725,081, 6,767,327, 6,776,763, 6,779,257, 6,780,157,6,899,682, 6,962,567, 6,976,965, 7,097,620, 7,226,417, 7,641,480,7,676,910, 7,711,413, and 7,736,317, each of which is herebyincorporated by reference in its entirety.

In alternate embodiments, the imaging apparatus 980 may be or include,by way of non-limiting example, any of grey-scale IVUS, forward-lookingIVUS, rotational IVUS, phased array IVUS, solid state IVUS,spectroscopy, or optical coherence tomography. It is understood that, insome instances, wires associated with the imaging apparatus extend alongthe length of the elongated tubular body through the handle and alongelectrical connection to the interface such that signals from theimaging apparatus can be communicated to the controller. In someinstances, the imaging apparatus communicates wirelessly with thecontroller and/or the processor.

The devices, systems, and methods described herein may be used tocharacterize tissue and provide real-time feedback as to the level ofablation during a variety of diagnostic, ablation and/or neuromodulationapplications, including without limitation: carotid body ablation,cardiac ablation (including myocardial), renal neuromodulation,intravascular lesion ablation, and chronic total occlusion crossing. Ineach of these embodiments, the database or memory would be configured tocontain pre-determined tissue imaging properties and secondaryparameters associated with particular types of tissue at varying levelsof ablation. The imaging apparatus utilizes this database 245 to compareand correlate the signal properties of the tissue-of-interest with thepre-determined properties to accurately characterize the tissue.

Referring now to FIG. 7, there is shown a partial cross-sectional viewof a blood vessel 700 with a lesion 712 partially occluding lumen 710.The lesion 712 has disrupted the intimal layer 714 and in variouslocations has disrupted the medial layer 716 such that there is nodistinguishable boundary between the medial layer 716 and theadventitial layer 718. Utilizing the tissue characterization techniquesdiscussed above, the small arterioles (vasa vasorum and neo vasavasorum) in the adventitial or medial layers may be distinguished. Inone aspect, the flow of fluid within the small arterioles can bedetected by changes between different scans such that a characterizationtechnique can determine the presence, location and extent of thearterioles 720. As shown in FIG. 7, traditional tissue characterizationtechniques would provide information concerning the make-up and lengthL1 of lesion 712. Based on this information, a stent may be deployedbased on the length L1 to treat the lesion and restore effective bloodflow through lumen 710. Unfortunately, already distressed vessel wallson either end of the stent may continue with disease progression andform a further blockage adjacent a stent. Utilizing tissuecharacterization outside the intimal layer 714, the arterioles can beimaged and characterized as an indication of the extent of diseaseprogression. Based on this additional information, it can be determinedthat a much greater length L2 of the vessel is responding to distress bythe growth of arterioles to supply oxygen for continued cell growth.

Referring now to FIGS. 8A and 8B, there is shown a pair of angiographicimages illustrating the impact of myocardial bridging on a coronaryartery 810. In FIG. 8A, the coronary artery 810 is shown during thecontraction of the heart with the myocardial bridging occurring betweenthe arrows A substantially decreasing the volume of blood that can passthrough the coronary artery. In FIG. 8B, the heart muscle is in arelaxed state thereby allowing substantially complete flow of bloodthrough the coronary artery 810′. This condition is often very difficultto image utilizing standard angiography. Utilizing an imaging system 110similar to the one disclosed with respect to FIG. 1, the coronary arteryin the area of the myocardial bridging can be imaged to better determinethe extent of the myocardium encroachment and determine the bestapproach for a therapeutic treatment. Although myocardium usuallyappears echolucent on gray scale images configured for imaging intimalplaques, the imaging system 110 may be configured to utilize an imagingenergy or direction that is better suited to image the adventitialtissues surrounding the vessel lumen to detect myocardial bridging.Referring to FIGS. 9A and 9B, the cross-sectional image of the coronaryartery 810 shows a normal intima 820 and media 822, but myocardium 830surrounds greater than 50 percent of the circumference of the vessel andin some locations 834 has direct contact with the adventitia. Inadjacent regions, the myocardium overlies the artery but is spaced fromthe border 826 of the adventitia 824. While the myocardium is shown as asingle band of muscle, it will be appreciated that the myocardium may becomposed of a number of separate fibers. Thus, utilizing adventitialtissue characterization, including the perivascular tissues, healthcareproviders can better determine the location and extent of myocardialbridging about coronary vessels. As explained above, a 2-dimensionalimage or 3-dimensional model may be displayed illustrating the detectedpresence of myocardial tissue in the adventitial tissues.

Referring now to FIG. 10, there is shown a partial cross-sectional sideview of a vessel 1000 with a stent 1010 placed therein. The stent 1010is positioned in abutting relation with the vessel wall 1002. FIG. 11Ashows a first axial cross-sectional view taken along line 11-11 in FIG.10. In FIG. 11A, the image is divided by line M to represent the initialimplantation orientation to the left and vessel changes after the stenthas been implanted for a significant period of time on the right. Withreference to the initial implantation portion, stent strut 1004 is inintimate contact with vessel wall 1002, while stent strut 1006 is spacedfrom the vessel wall forming a void 1008. The vessel, including thestent, can then be imaged by an imaging system such as shown in FIG. 1.In one aspect, the memory 245 includes imaging characteristics andproperties associated with a variety of stents implanted within vessels.In one feature, the user is prompted to input the stent model andlength, which if matching stored look-up data, allows more efficientcharacterization of the stent material and surrounding tissues. Thecharacterization application 250 then compares the return ultrasoundechoes taken of the vessel 1000 with the implanted stent 1010. In oneaspect, the relatively bright return echoes from the stent can besubtracted from the other echoes such that tissue adjacent the strutscan be more effectively imaged. For example, the characterization systemmay more clearly recognize the void 1008 once the bright strut returnshave been removed. The characterizations conducted upon initialimplantation can be stored for later use.

Referring to the right half of FIG. 11A representing the stent afterindwelling for a significant time period, it can be seen that plaque1009 has formed around stents 1004′ and 1006′. An imaging system may bereinserted into the vessel having the stent 1010 and additional imaginginformation can be generated. In addition to characterization of thereturn information as set forth above, the characterization application250 can compare characterizations performed during initial implantationto those obtained after the stent has been indwelling for an extendedperiod. Although the intense returns off of the stent struts tend toobscure other structures, by subtracting the stent strut returns basedon lookup data in the memory 245 or prior scans of the same region,other structures such as plaque 1009 can now be more effectively imagedand characterized. The difference between original characterization andthe new characterization data can be displayed visually for the user.

FIG. 11B illustrates an alternative embodiment of the stent 1010′implanted within the vessel wall 1002. The stent 1010′ has stent strutscoated with a bioresorbable drug eluting coating. As shown on the leftside of line M, when initially implanted stent struts 1012, 1014 havebioresorbable coatings 1013, 1015, respectively. Information concerningthe thickness of the coatings and/or the struts themselves may beobtained from the manufacturer and stored in memory 245 or it may beobtained by scanning the stent after placement and determining theproperties by characteristics techniques as discussed above. Asillustrated by the right half of FIG. 11B, after the stent 1010′ hasbeen indwelling for a significant period of time the coatings with be atleast partially resorbed by the body. As shown on the right side of lineM′, strut 1012′ still has a coating 1013′, although the coating has beenreduced substantially in thickness. In contrast, the coating on strut1014′ has completely dissolved and is no longer present. The lack of adrug eluting coating may also be indicated where plaque 1009′ has formedon the now bare metal stent struts. Consistent with the disclosureabove, an imaging system may be positioned within the bioresorbablestent to image the stent after indwelling for a period of time. Acharacterization technique can compare the sensed bioresorbable coatingwith the initial coating thickness to provide the user with anestimation of how much of the coating dissolved over the given period ofimplantation along with an estimation of how much longer the drugeluding bioresorbable coating may continue to be effective for thepatient.

Referring now to FIG. 11C, there is shown a further alternative stent1010″ representing a stent formed of a bioresorbable material such thatthe stent struts 1020 and 1022 dissolve in the body over time. Asdescribed above the bioresorbable scaffold of stent 1010″ may be imagedby an imaging device and the resulting scan and/or characterizationstored for later use. As part of the characterization process,manufacturer information about the stent can be utilized to provide abetter, more accurate characterization of the sensed stent and tissueinformation. After the stent has been indwelling for a period of time,an imaging system may be positioned within the bioresorbable stent toimage the stent and surrounding tissue. A characterization technique cancompare the detected bioresorbable material of struts 1020′ and 1022′along with the surround tissue structures with the savedcharacterizations from the initial implantation. The changes in bothstent strut dimension and surrounding tissue identified during thecharacterization process can be displayed for a user.

Referring now to FIG. 12A, there is shown a vessel 1200 with anocclusion 1212 that totally occludes side branch 1210. As discussedabove and shown more fully in FIG. 7, the plaque forming the occlusion1212 often disrupts the intima and the media, along with the media andadventitia boundary making plaque segmentation or border detectiondifficult. Still further, when using forward looking imaging, the angleof incidence between the emitted signals and the vessel tissue makeborder detection difficult. In one embodiment according to the presentdisclosure, an imaging device images the adventitia of a vessel tothereby assist the user in determining a safe path for crossing theocclusion. In one example, a forward looking imaging catheter 1250 isinserted into the vessel 1200. The catheter 1250 is advanced to the sidebranch 1210 with the imaging element 1252 energized to visual thestructures in front of the catheter. In the position shown in FIG. 12A,the catheter tip is oriented along longitudinal axis L12 creating fieldof view FV12. As shown more fully in FIG. 12B, the field of viewdisplays a portion of the lumen 1220, the occlusion 1212 and theadventitial tissue 1222. Utilizing the tissue characterizationtechniques discussed above, the system can provide a display to a userin virtually real time to show the user whether the selected pathintersects adventitial tissue thereby leading to a rupture of thevessel. As shown in FIG. 12B, while the longitudinal axis L12 passesthrough the occlusion 1212, it also dissects adventitia 1222 such thatthe proposed path is a poor choice and should be avoided by the user.

Referring now to FIG. 13A, the forwarding looking imaging catheter 1250has been repositioned in vessel 1200 such that the longitudinal axis L13extends at a different angle with respect to side branch 1210. As shownmore fully in FIG. 13B, the field of view display FV13 shows that thedevice is oriented along longitudinal axis L13 to extend acrossocclusion 1212 and remain within lumen 1220 of the side branch 1210.Tissue characterization is utilized to identify the adventitial tissue1222 that is displayed on the borders of the field of view. In thismanner, imaging and tissue characterization of the adventitial tissuecan be utilized to define a path across the occlusion. While illustratedin terms of utilization of a forward looking imaging system, a similartechnique can be utilized with side looking imaging devices.

Referring now to FIGS. 14A and 14B, there is shown a furtherforward-looking image device and representative vessel image. Theimaging system 1400 includes a catheter body 1402 with an ultrasonictransducer 1404 oriented to extend at an angle, for example 45 degrees,with respect to the longitudinal axis such that when the transducer isrotated around the catheter longitudinal axis a conical imaging area1406 is created. This type of device may be used in a manner similar tothe system discussed with respect to FIGS. 12A-13B. More specifically,an output image 1408 may be generated that can display the results of atissue characterization analysis to display to the user the adventitiatissue and/or boundaries between adjacent tissue types. As explainedabove, when the adventitia tissue is displayed on the border of thedisplayed image, the area in front of the catheter may be entered tocross a chronic total occlusion.

While the present invention has been illustrated by the description ofembodiments thereof, and while the embodiments have been described inconsiderable detail, it is not the intention of the applicants torestrict or in any way limit the scope of the appended claims to suchdetail. Additional advantages and modifications will readily appear tothose skilled in the art. Therefore, the invention, in its broaderaspects, is not limited to the specific details, the representativeapparatus, and illustrative examples shown and described. Accordingly,departures may be made from such details without departing from thespirit or scope of the applicant's general inventive concept.

Persons of ordinary skill in the art will appreciate that theembodiments encompassed by the present disclosure are not limited to theparticular exemplary embodiments described above. In that regard,although illustrative embodiments have been shown and described, a widerange of modification, change, and substitution is contemplated in theforegoing disclosure. It is understood that such variations may be madeto the foregoing without departing from the scope of the presentdisclosure. Accordingly, it is appropriate that the appended claims beconstrued broadly and, in a manner, consistent with the presentdisclosure.

What is claimed is:
 1. An intravascular system, comprising: a processorconfigured for communication with an intravascular imaging catheteroperable to obtain image data of a blood vessel, wherein the processoris configured to: receive the image data of the blood vessel obtained bythe intravascular imaging catheter; perform a pattern recognition of theimage data to characterize adventitial tissue of the blood vessel;output, to a display in communication with the processor, an image ofthe blood vessel based on the image data; and alert a user to a presenceof the adventitial tissue in real time based on the characterization ofthe adventitial tissue and a positioning of a therapy device within theblood vessel to avoid rupturing the blood vessel.
 2. The intravascularsystem of claim 1, further comprising: the therapy device, wherein thetherapy device is operable to perform a therapy while positioned withinthe blood vessel and be repositioned in response to the alerting.
 3. Theintravascular system of claim 2, wherein the therapy device comprises achronic total occlusion crossing device.
 4. The intravascular system ofclaim 2, wherein the therapy device comprises an ablation device.
 5. Theintravascular system of claim 1, wherein the pattern recognition of theimage data comprises comparing the image data to a pattern recognitiondatabase.
 6. The intravascular system of claim 5, wherein the patternrecognition database comprises information associated with at least oneof a size associated with the adventitial tissue, nerve celldirectionality, vasa vasorum directionality, a morphology, or patientdemographic information.
 7. The intravascular system of claim 5, whereinthe pattern recognition database comprises signal properties associatedwith a frequency or a harmonic pattern corresponding to the image data.8. The intravascular system of claim 1, wherein the pattern recognitioncomprises at least one of a classification tree, a random forest, aneural network, a regression tree, or a principal component.
 9. Theintravascular system of claim 1, wherein the processor is configured toalert the user of the presence of the adventitial tissue by outputting,to the display, a graphical indicator identifying a portion of the imageof the blood vessel corresponding to the adventitial tissue.
 10. Theintravascular system of claim 9, wherein the graphical indicatorcomprises a colorization of the portion of the image of the blood vesselcorresponding to the adventitial tissue.
 11. The intravascular system ofclaim 1, wherein the image of the blood vessel comprises amulti-dimensional model of the blood vessel constructed based on theimage data.
 12. The intravascular system of claim 1, further comprisingthe intravascular imaging catheter.
 13. The intravascular system ofclaim 1, further comprising the display.